The Brain and Cholesterol Portrait of the Niemann Pick’s Disease: The mothers’ chorus

Chapter 1- The hurricane: Bewilderment, fear, sleepless nights that never seemed to end. Words pounding in my head: neurodegeneration, cholesterol homeostasis, rare disease, mutation, and the worst, no cure. Yes, the diagnosis was a relief of sorts. And yes, it was hell - to face the suffering and inevitable death of my child. A genetic disease! We didn't do anything wrong. Still, culpability haunted us. After all, I passed on a mutated gene to him and so did his father. It is painful and natural, a terrible incident, two mutant versions coming together - by chance!


Chapter 2- The facts: At the age of 3 our son started stuttering. At age 5 he had problems manipulating things with his hands. At school, he started to forget what he just had learnt, he couldn't control his movements anymore and he lost his ability to speak. Psychomotor problems? Mental retardation? Neurodegeneration? At this point, we were beside ourselves with worry. We went to dozens of doctors, received countless diagnoses, and tried all sorts of remedies - nothing. And somewhat like a dark version of Benjamin Button’s movie, our big boy became apathic, silent, confined to a wheelchair. He was 10 and we felt something was looming ahead - darkness. We weren’t ready for it.


Chapter 3- The Science: Niemann Pick’s Disease Type C, or NP-C in short - is a rare disease affecting about one birth in 100,000 with a very wide range of disease onset, severity and lifespan. Some kids die within a few months after birth; most become sick when they enter school with an average lifespan of up to ten years. An unknown number of patients survive into adulthood and many of them spend their life in psychiatric hospitals without proper diagnosis.


What's going awry? It's all about cholesterol! Yes, you read correctly, we are talking about cholesterol in the brain. Cells there – as anywhere else in our bodies, by the way – need cholesterol to function properly. Normally cholesterol enters cells via the bloodstream and is carried to parts of the cell that need it. But in Niemann Pick’s Disease, this “trafficking” goes wrong. The cholesterol builds up in cells and body tissues, including the brain, which cannot handle all the fat, and so nerve cells die. It’s like a train wreck…


The mechanisms causing NP-C are far from being elucidated. Some groups try to understand why neurons are so vulnerable to the defect. Others try to develop therapies to stop the disease progression and new diagnostic approaches to detect the disease as early as possible. As it has often been stated: the eye is a window to the brain. The Pfrieger group uses the retina to address these topics. Yet much more is still to be discovered at this stage.


Chapter 4- Acceptance: Genetic diseases are brutal, condemning. A mix of guilt and helplessness nibbled at me inside for a long time. My release from such an unhealthy state was meeting scientists like Dr. Pfrieger. Scientists stand amidst patients, families, and doctors. They can help us to understand and thus cope with the disease by explaining the biology behind it - as far as possible - and they can indicate possible therapeutic strategies to keep the hope alive.


This short story introduces us to the NP-C genetic disease, and on a greater sphere, it conducts us to reflect on the importance of medical research. Frank Pfrieger is a senior researcher affiliated with the Institute of Cellular and Integrative Neurosciences of the Centre National de la Recherche Scientifique and the University of Strasbourg. The topic is his current line of research, which is funded by the CNRS, the University and mostly by patient associations.


Text by Fernanda Haffner

Illustration by Marion Couturier